# JAK1

Source: https://onco.cc/targets/jak1/  
OnCo record `jak1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

JAK1 is one of the kinases that pass cytokine and interferon signals inside immune and blood cells. Ruxolitinib and momelotinib block JAK1 together with JAK2 to calm the inflammation of myelofibrosis; golidocitinib is the first JAK1-only inhibitor approved for a cancer, in peripheral T-cell lymphoma.

## Summary

JAK1 (chromosome 1p31.3) is a non-receptor tyrosine kinase that phosphorylates the signal-transducing subunits of cytokine receptor complexes including IL2RB, IL10RA, IFNAR2, IL6ST, LIFR, OSMR and IL31RA; it is required for interferon alpha, beta and gamma signalling, where it phosphorylates IFNAR2 to create STAT docking sites, and it activates STATs directly or through partner JAK kinases (UniProt P23458). In OnCo, JAK1 is inhibited with JAK2 by ruxolitinib and momelotinib for spleen and symptom control in myelofibrosis, deliberately spared by pacritinib to limit myelosuppression, and selectively targeted by golidocitinib, approved in China in 2024 for relapsed peripheral T-cell lymphoma.

## Fields

- Kind: Target
- Last checked: 2026-09-22
- Also known as: Janus kinase 1; JAK1A; JTK3
- Tags: wave5-target
- Symbol: JAK1
- Class: kinase
- Biology: The JAK-STAT pathway record notes that interferon-gamma signalling through JAK1/2 and STAT1 raises MHC and PD-L1 expression, and that JAK1/2 loss-of-function mutations cause acquired resistance to PD-1 blockade, so JAK1 is both a drug target in blood cancers and a resistance gene in immunotherapy.
- Where found: Myelofibrosis and other myeloproliferative neoplasms (JAK1/2 inhibitors); Peripheral T-cell lymphoma (golidocitinib); Tumours with JAK1 loss (checkpoint resistance)

## Notes

- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
- Lymphoma, JAK-STAT, in NK/T-cell lymphoma and in Hodgkin lymphoma: STAT3 and STAT5B mutations lock the transcription factor in its phosphorylated form. The STAT5B N642H substitution increases the binding affinity of the phosphotyrosine for the mutant histidine, so the phosphorylated protein persists and binds its target sites far more, and the growth advantage it gives can be partly reversed by a JAK1/2 inhibitor in the laboratory (Kucuk 2015). In Hodgkin lymphoma and primary mediastinal B-cell lymphoma the pathway is switched on from the other end, by amplification of JAK2 inside the 9p24.1 amplicon and by loss of the brakes SOCS1 and PTPN1. Frequency: Activating STAT3 and STAT5B mutations across 51 NK/T-cell lymphomas and 43 gamma-delta T-cell lymphomas, with STAT5B N642H particularly frequent in the gamma-delta group (Kucuk 2015). JAK2 sits in the 9p24.1 amplicon in Hodgkin lymphoma and mediastinal large B-cell lymphoma, and its amplification raises both protein and activity and specifically induces PD-1 ligand transcription (Green 2010). What it changes about treatment: Not through an approved drug. JAK inhibitors have been tested in both settings without becoming standard; the practical consequence of the Hodgkin and mediastinal finding is that it explains why checkpoint blockade works there.

## Sources

- HGNC HGNC:6190: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6190
- UniProt P23458: https://www.uniprot.org/uniprotkb/P23458/entry
- NCBI Gene 3716: https://www.ncbi.nlm.nih.gov/gene/3716
- Kucuk et al., Nat Commun 2015: activating STAT3 and STAT5B mutations in lymphomas derived from NK or gamma-delta T cells: https://doi.org/10.1038/ncomms7025
- Green et al., Blood 2010: selective 9p24.1 amplification and PD-1 ligand induction through JAK2 in Hodgkin lymphoma and mediastinal large B-cell lymphoma: https://doi.org/10.1182/blood-2010-05-282780

## Connected records

- drugs: [Golidocitinib](https://onco.cc/drugs/golidocitinib/), [Momelotinib](https://onco.cc/drugs/momelotinib/), [Pacritinib](https://onco.cc/drugs/pacritinib/), [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/)
- targets: [JAK2](https://onco.cc/targets/jak2/)
- cancers: [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/), [Myeloproliferative neoplasms (PV, ET, myelofibrosis)](https://onco.cc/cancers/myeloproliferative-neoplasms/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Primary myelofibrosis](https://onco.cc/cancers/primary-myelofibrosis/), [Sezary syndrome](https://onco.cc/cancers/sezary-syndrome/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- pathways: [Antigen presentation & immune editing](https://onco.cc/pathways/antigen-presentation-immunoediting/), [JAK-STAT signalling](https://onco.cc/pathways/jak-stat/)

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